The objective is to gain precise knowledge of certain cell surface markers especially those of lymphoid cells, and how each can serve as a differentiation signal or trigger the activities of another cell. Most of the effort is directed at components of the major histocompatibility complex of man, HLA, which includes two distinct types of antigen, Class I and Class II. Only 3 Class I molecules have been identified although over 30 genes exist. One of our aims is to determine if other genes in this cluster (which we call a congener) are operational in cells of certain tissue such as thymus or vascular endothelium or if some develop only at specific stages of differentiation. Another aim is to produce monoclonal antibodies to the Class I and Class II antigens. The Class II congener includes at least 9 functioning genes but only 3 or 4 of the products, transmembranous glycoprotein heterodimers can clearly be distinguished. Having produced monoclonal antibodies to at least some of the individual Class II glycoproteins and to the 2 or more epitopes probably carried by each, we wish to know if each molecule has separate function and we ask the complementary question "do the different epitopes of the same molecule even have different function". We believe that the answers to these questions will help us understand why some people form antibodies after transfusion and some do not, why some reject kidneys and others do not, and how we might, through such detailed analyses understand and control immune responses in health and in diseases such as AIDS and autoimmunity. Since we can learn about cellular function by an analysis of mutant cells, we propose to screen for somatic mutants. We shall also look for new markers of B lymphocytes and plasma cells. In a separate series of experiments in mice we plan to study the way that the MHC molecules are transported to the surface of the phagocytic cell since this may help us understand the way that highly complex molecules function as antigens.